A Phase I, Open Label, Maximum Tolerated Dose-Finding Study to Evaluate the Safety and Tolerability of 90Y-DOTA-tyr3-Octreotide Administered by Intravenous Infusion to Children With Refractory Somatostatin-Receptor Positive Tumors

Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide administered by intravenous infusion to children with refractory somatostatin-receptor positive tumors based upon the 6 week/cycle dose-limiting-toxicity profile.

Evaluate the short term and long term safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events) [ Time Frame: short term (6 weeks/cycle); long term (4-6 mos./cycle) ]

Dose escalation will proceed so that the single-cycle and three-cycle maximum tolerated doses of 90Y-DOTA-tyr3-Octreotide can be determined. The initial dose of 90Y-DOTA-tyr3-Octreotide to be administered is 30 mCi/m2 in each of three cycles. Dose escalation will proceed in 10 mCi/m2 intervals and will be permitted for the next cohort of subjects pending completion of Cycle 3 by 2 members of the previous cohort with no DLTs. A DLT is defined as a Grade 3 renal toxicity, Grade 4 bone marrow toxicity, or any other Grade 3 toxicity whether or not related to study drug and regardless of duration. Lymphopenia will not be used to define a DLT.

Radiation: 90Y-DOTA-tyr3-OCTREOTIDE

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of yttrium Y 90-DOTA-tyr3-octreotide in children with advanced or refractory somatostatin receptor-positive tumors.

Determine the short-term and long-term safety and the serious adverse-event profiles of this drug in these patients.

Determine any potential antitumor effect of this drug in these patients.

Correlate level of somatostatin receptor type 2 expression with response in patients treated with this drug.

OUTLINE: This is a dose-escalation study.

Patients receive yttrium Y 90-DOTA-tyr3-octreotide IV over 5-10 minutes on day 1. Treatment repeats every 6 weeks for up to 3 courses in the absence of unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of yttrium Y 90-DOTA-tyr3-octreotide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed weekly after each treatment course, 6 weeks after the last course, and then every 6 months thereafter for life.

PROJECTED ACCRUAL: Approximately 25-35 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:

2 Years to 25 Years (Child, Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed malignant neoplasm

Not amenable to standard therapy or has failed existing first- and second-line therapies

Tumor positive for somatostatin receptors by OctreoScan within the past 4 weeks

At least 1 measurable lesion

Lesions that have been previously irradiated must demonstrate progression since radiation

At least 1 measurable somatostatin receptor-positive lesion that has not been irradiated within the past 4 weeks AND has not had full craniospinal radiation within the past 3 months

Bone marrow with at least 40% cellularity OR at least 20% cellularity with one million CD34+ stem cells/kg stored

No diffuse bone marrow involvement by OctreoScan scintigraphy

PATIENT CHARACTERISTICS:

Age

2 to 25

Performance status

COG 0-2 OR

Karnofsky 60-100% OR

Lansky 60-100%

Life expectancy

2-12 months

Hematopoietic

See Disease Characteristics

Absolute neutrophil count at least 1,000/mm^3

Platelet count at least 100,000/mm^3

Hepatic

Bilirubin less than 1.5 times normal

AST and ALT less than 2.5 times upper limit of normal

Renal

Creatinine no greater than 1 mg/dL (children less than 5 years of age)

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00049023